title: Granulocyte-macrophage colony-stimulating factor (GM-CSF): a chemoattractive agent for murine leukocytes in vivo.
abstract: GM-CSF is well recognized as a proliferative agent for hematopoietic cells and exerts a priming function on neutrophils. The aim of this study was to determine if GM-CSF has a role as a neutrophil chemoattractant in vivo and if it can contribute to recruitment during intestinal inflammation. Initial studies in vitro, using the under-agarose gel assay, determined that GM-CSF can induce neutrophil migration at a much lower molar concentration than the fMLP-like peptide WKYMVm (33.5-134 nM vs. 1-10 μM). GM-CSF-induced neutrophil migration was ablated (<95%) using neutrophils derived from GMCSFRβ(-/-) mice and significantly attenuated by 42% in PI3Kγ(-/-)neutrophils. In vivo, a significant increase in leukocyte recruitment was observed using intravital microscopy 4 h post-GM-CSF (10 μg/kg) injection, which was comparable with leukocyte recruitment induced by KC (40 μg/kg). GM-CSF-induced recruitment was abolished, and KC-induced recruitment was maintained in GMCSFRβ(-/-) mice. Furthermore, in vivo migration of extravascular leukocytes was observed toward a gel containing GM-CSF in WT but not GMCSFRβ(-/-) mice. Finally, in a model of intestinal inflammation (TNBS-induced colitis), colonic neutrophil recruitment, assessed using the MPO assay, was attenuated significantly in anti-GM-CSF-treated mice or GMCSFRβ(-/-) mice. These data demonstrate that GM-CSF is a potent chemoattractant in vitro and can recruit neutrophils from the microvasculature and induce extravascular migration in vivo in a β subunit-dependent manner. This property of GM-CSF may contribute significantly to recruitment during intestinal inflammation.
authors.affiliation: Institute of Inflammation, Infection and Immunity, Gastrointestinal Research Group, Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada.
authors.forename: Maitham
authors.initials: M
authors.lastname: Khajah
authors.forename: Brandie
authors.initials: B
authors.lastname: Millen
authors.forename: Denise Carmona
authors.initials: DC
authors.lastname: Cara
authors.forename: Christopher
authors.initials: C
authors.lastname: Waterhouse
authors.forename: Donna-Marie
authors.initials: DM
authors.lastname: McCafferty
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology*; D053648:Cytokine Receptor Common beta Subunit / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002630:Chemotactic Factors; D053648:Cytokine Receptor Common beta Subunit; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009195:Peroxidase; D019869:Phosphatidylinositol 3-Kinases